Abstract

Both BRCA1 and BRCA2 proteins play a role in DNA damage response, and their deficiency leads to chromosomal instability and carcinogenesis. Hereditary mutations in either of these genes increase strikingly the lifetime risk of breast and ovarian cancer and to a lesser extent the risk of males’ breast and prostate cancer and of pancreatic cancer. It is generally accepted that when treated by standard therapy, the prognosis of BRCA- mutated breast cancer patients is equivalent to that of patients with sporadic disease. Increased sensitivity of BRCA-associated breast cancer to DNA damaging chemotherapy, especially platinum compounds, was demonstrated in preclinical models and in clinical trials. However, definitive evidence that would justify their advancement to clinical practice is lacking. Inhibitors of poly (ADP-ribose) polymerase target BRCA-deficient cells specifically. Multiple clinical trials with these compounds are ongoing, although none made its way to clinical practice yet. Hopefully, ongoing clinical research would eventually result in better treatment and improved prognosis.

Goodwin PJ, Phillips KA, West DW, et al. Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study. J Clin Oncol. 2012;30:19–26. A large population based trial demonstrated similar outcomes in BRCA1 mutation carriers and patients with sporadic disease. BRCA2 mutation carriers had worse prognosis than patients with sporadic disease at the same age, but similar when analysis was adjusted for the effects of tumor- and treatment-related variables.PubMedCrossRefGoogle Scholar